Direct Comparison Meta-analysis Research Articles

Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis.

The aim of this study was to evaluate the effect of intraoperative botulinum toxin (BT) injection on delayed gastric emptying (DGE) and need for endoscopic pyloric intervention (NEPI) following esophagectomy. In compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards, a systematic review of studies reporting the outcomes of intraoperative BT injection in patients undergoing esophagectomy for esophageal cancer was conducted. Proportion meta-analysis model was constructed to quantify the risk of the outcomes and direct comparison meta-analysis model was constructed to compare the outcomes between BT injection and no BT injection or surgical pyloroplasty. Meta-regression was modeled to evaluate the effect of variations in different covariates among the individual studies on overall summary proportions. Nine studies enrolling 1070 patients were included. Pooled analyses showed that the risks of DGE and NEPI following intraoperative BT injection were 13.3% (95% confidence interval [CI]: 7.9-18.6%) and 15.2% (95% CI: 7.9-22.5%), respectively. There was no difference between BT injection and no BT injection in terms of DGE (odds ratio [OR]: 0.57, 95% CI: 0.20-1.61, P = 0.29) and NEPI (OR: 1.73, 95% CI: 0.42-7.12, P = 0.45). Moreover, BT injection was comparable to pyloroplasty in terms of DGE (OR: 0.85, 95% CI: 0.35-2.08, P = 0.73) and NEPI (OR: 8.20, 95% CI: 0.63-105.90, P = 0.11). Meta-regression suggested that male gender was negatively associated with the risk of DGE (coefficient: -0.007, P = 0.003). In conclusion, level 2 evidence suggests that intraoperative BT injection may not improve the risk of DGE and NEPI in patients undergoing esophagectomy. The risk of DGE seems to be higher in females and in early postoperative period. High quality randomized controlled trials with robust statistical power are required for definite conclusions. The results of the current study can be used for hypothesis synthesis and power analysis in future prospective trials.

Surgical interventions for symptomatic knee osteoarthritis: a network meta-analysis of randomized control trials

BackgroundMultiple surgical interventions exist for the treatment of symptomatic knee osteoarthritis, but the surgeon and patient may often have difficulty deciding which interventions are the best option.MethodsWe conducted a systematic review to identify randomized clinical trials (RCTs) that compared complications, revisions, reoperations, and functional outcomes among TKA (total knee arthroplasty), UKA (unicompartmental knee arthroplasty), HTO (high tibial osteotomy), BCA (bicompartmental knee arthroplasty), BIU (bi-unicompartmental knee arthroplasty), and KJD (knee joint distraction). The PubMed, Embase, and Cochrane databases were reviewed for all studies comparing two or more surgical interventions. Direct-comparison meta-analysis and network meta-analysis (NMA) were performed to combine direct and indirect evidence. The risk of bias was assessed using the revised Cochrane risk of bias tool for RCTs.ResultsThis NMA and systematic review included 21 studies (17 RCTs), with a total of 1749 patients. The overall risk-of-bias assessment of the RCTs revealed that 7 studies had low risk, 5 had some concerns, and 9 had high risk. SUCRA (the surface under the cumulative ranking curve) rankings revealed that KJD had the greatest risk of appearing postoperative complications, revisions, and reoperations, and UKA or TKA had the lowest risk. The majority of comparisons among various treatments showed no difference for functional outcomes.ConclusionEach surgical intervention is noninferior to other treatments in functional outcomes, but UKA and TKA are better options to treat OA according to SUCRA rankings by comparing complications, revisions, and reoperations. KJD is an imperfect option for treating OA. Other treatments should be carefully considered for each patient in accordance with their actual conditions. However, this conclusion is limited by the selection of reviewed publications and individual variation of surgical indications for patients.Trial registrationThis study was registered with Research Registry (reviewregistry1395).

A Systematic Review of the Efficacy and Safety of Ketamine in Total Joint Arthroplasty

BackgroundKetamine is administered intraoperatively to treat pain associated with primary total hip (THA) and knee arthroplasty (TKA). The purpose of this study was to evaluate the efficacy and safety of ketamine in primary THA and TKA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons (AAHKS), American Academy of Orthopaedic Surgeons (AAOS), Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management (ASRA). MethodsThe MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to 2020 on ketamine in THA and TKA. All included studies underwent qualitative assessment and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of ketamine. After a critical appraisal of 136 publications, 7 high-quality studies were included for analyses. ResultsHigh-quality evidence demonstrates that intraoperative ketamine decreases postoperative opioid consumption. Four of 7 studies found that ketamine reduces postoperative pain. Intraoperative ketamine is not associated with an increase in adverse events and may reduce postoperative nausea and vomiting (relative risk [RR] 0.68; 95% CI 0.50-0.92). ConclusionHigh-quality evidence supports the use of ketamine intraoperatively in THA and TKA to reduce postoperative opioid consumption. Most studies found ketamine reduces postoperative pain, nausea, and vomiting. Moderate quality evidence supports the safety of ketamine, but it should be used cautiously in patients at risk for postoperative delirium, such as the elderly.

The Efficacy and Safety of Corticosteroids in Total Joint Arthroplasty: A Direct Meta-Analysis

BackgroundCorticosteroids are commonly used intraoperatively to treat pain and reduce opioid consumption and nausea associated with primary total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of corticosteroids in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management. MethodsThe MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published before February 2020 on corticosteroids in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of corticosteroids. ResultsCritical appraisal of 1,581 publications revealed 23 studies regarded as the best available evidence for analysis. Intraoperative dexamethasone reduces postoperative pain, opioid consumption, and nausea and vomiting. Multiple doses lead to further reduction in pain, opioid consumption, nausea and vomiting. There is insufficient evidence on the risk of adverse events with perioperative dexamethasone in TJA. ConclusionStrong evidence supports the use of a single dose or multiple doses of intravenous dexamethasone to reduce postoperative pain, opioid consumption, nausea and vomiting after primary TJA. There is insufficient evidence on perioperative dexamethasone in primary TJA to determine the optimal dose, number of doses, or risk of postoperative adverse events.

The Efficacy and Safety of Regional Nerve Blocks in Total Knee Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundRegional nerve blocks are widely used in primary total knee arthroplasty (TKA) to reduce postoperative pain and opioid consumption. The purpose of our study was to evaluate the efficacy and safety of regional nerve blocks after TKA in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published before March 24, 2020 on femoral nerve block, adductor canal block, and infiltration between Popliteal Artery and Capsule of Knee in primary TKA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of the regional nerve blocks compared to a control, local peri-articular anesthetic infiltration (PAI), or between regional nerve blocks. ResultsCritical appraisal of 1,673 publications yielded 56 publications representing the best available evidence for analysis. Femoral nerve and adductor canal blocks are effective at reducing postoperative pain and opioid consumption, but femoral nerve blocks are associated with quadriceps weakness. Use of a continuous compared to single shot adductor canal block can improve postoperative analgesia. No difference was noted between an adductor canal block or PAI regarding postoperative pain and opioid consumption, but the combination of both may be more effective. ConclusionSingle shot adductor canal block or PAI should be used to reduce postoperative pain and opioid consumption following TKA. Use of a continuous adductor canal block or a combination of single shot adductor canal block and PAI may improve postoperative analgesia in patients with concern of poor postoperative pain control.

The Efficacy and Safety of Periarticular Injection in Total Joint Arthroplasty: A Direct Meta-Analysis

BackgroundPeriarticular injection (PAI) is administered intraoperatively to help reduce postoperative pain and opioid consumption after primary total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of PAI in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Medicine. MethodsThe MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to March 2020 on PAI in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of PAI. ResultsThree thousand six hundred and ninety nine publications were critically appraised to provide 60 studies regarded as the best available evidence for an analysis. The meta-analysis showed that intraoperative PAI reduces postoperative pain and opioid consumption. Adding ketorolac or a corticosteroid to a long-acting local anesthetic (eg, ropivacaine or bupivacaine) provides an additional benefit. There is no difference between liposomal bupivacaine and other nonliposomal long-acting local anesthetics. Morphine does not provide any additive benefit in postoperative pain and opioid consumption and may increase postoperative nausea and vomiting. There is insufficient evidence to draw conclusions on the use of epinephrine and clonidine. ConclusionStrong evidence supports the use of a PAI with a long-acting local anesthetic to reduce postoperative pain and opioid consumption. Adding a corticosteroid and/or ketorolac to a long-acting local anesthetic further reduces postoperative pain and may reduce opioid consumption. Morphine has no additive effect and there is insufficient evidence on epinephrine and clonidine.

The Efficacy and Safety of Regional Nerve Blocks in Total Hip Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundRegional nerve blocks may be used as a component of a multimodal analgesic protocol to manage postoperative pain after primary total hip arthroplasty (THA). The purpose of our study was to evaluate the efficacy and safety of regional nerve blocks after THA in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published prior to March 24, 2020 on fascia iliaca, lumbar plexus, and quadratus lumborum blocks in primary THA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of the regional nerve blocks. ResultsAn initial critical appraisal of 3,382 publications yielded 11 publications representing the best available evidence for an analysis. Fascia iliaca, lumbar plexus, and quadratus lumborum blocks demonstrate the ability to reduce postoperative pain and opioid consumption. Among the available comparisons, no difference was noted between a regional nerve block or local periarticular anesthetic infiltration regarding postoperative pain and opioid consumption. ConclusionLocal periarticular anesthetic infiltration should be considered prior to a regional nerve block due to concerns over the safety and cost of regional nerve blocks. If a regional nerve block is used in primary THA, a fascia iliaca block is preferred over other blocks due to the differences in technical demands and risks associated with the alternative regional nerve blocks.

SP8.2.2 Neoadjuvant chemoradiotherapy (CRT) versus immediate surgery for resectable and borderline resectable pancreatic cancer: meta-analysis and trial sequential analysis of randomised controlled trials

Abstract Aims To compare resection and survival outcomes of CRT and immediate surgery in patients with resectable and borderline resectable pancreatic cancer Methods In compliance with PRISMA statement standards, electronic databases were searched to identify all randomised controlled trials (RCTs) investigating outcomes of neoadjuvant CRT versus immediate surgery in patients with resectable and borderline resectable pancreatic cancer. Two treatment strategies were compared using direct comparison meta-analysis model. Random effects modelling was applied to calculate pooled outcome data. The risks of Type1 or Type2 error in the meta-analysis model were assessed using trial sequential analysis (TSA) model. The certainty of evidence was assessed using GRADE system. Results 400 patients from 4 RCTs were included. When resectable and borderline resectable diseases were analysed together, neoadjuvant CRT resulted in higher R0 resection rate (RR: 1.55, P=0.004), longer overall survival (MD: 3.75, P=0.009) but lower overall resection rate (RR: 0.83, P=0.008). When resectable and borderline resectable diseases were analysed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, P=0.004) and overall survival (MD: 6.64, P=0.004) in patients with borderline resectable pancreatic cancer but it did not improve R0 resection rate (RR: 1.18, P=0.13) and overall survival (MD: 0.94, P=0.57) in patients with resectable pancreatic cancer. Conclusions Evidence from RCTs suggests that neoadjuvant CRT improves R0 resection rate and overall survival in patients with borderline resectable pancreatic cancer but not in patients with resectable pancreatic cancer. Nevertheless, the best available evidence does not include the contemporary chemotherapy regimens; therefore, more definite conclusions would depend on the results of future RCTs.

WE4.5 Meta-analysis of the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) for inguinal hernia

Abstract Aims To evaluate the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) in patients undergoing elective inguinal hernia repair Methods In compliance with PRISMA statement standards, electronic databases were searched to identify all studies reporting the outcomes of TREPP in patients undergoing elective inguinal hernia repair. The outcomes of interest included recurrence, chronic pain, haematoma, and wound infection. Proportion meta-analysis model was constructed to quantify the risk of postoperative complications and direct comparison meta-analysis model was constructed to compare the outcomes of TREPP and other open techniques. Random-effects modelling was applied to calculate pooled outcome data. Results Seven studies enrolling 1891 patients undergoing TREPP were included. Pooled analyses showed that TREPP was associated with 3.00% (95% CI 1.00–6.00%) risk of recurrence, 3.00% (95% CI 2.00–6.00%) risk of chronic pain, 8.00% (95% CI 0.00–20.00%) risk of haematoma, and 3.00% (95% CI 0.00–6.00%) risk of wound infection. The results remained consistent through subgroup analysis of patients with primary hernias and those with recurrent hernias. Analysis of a limited number of comparative studies showed no difference between TREPP and Lichtenstein technique in terms of recurrence (OR: 1.57, P=0.26) and chronic pain (OR: 1.16, P=0.59). Conclusions The best available evidence suggests that TREPP may be a promising technique for elective repair of inguinal hernias as indicated by low risks of recurrence, chronic pain, haematoma, and wound infection. Moreover, there is a lack of comparative evidence on outcomes of TREPP versus other techniques highlighting a need for high quality randomised controlled trials for definite conclusions.

Meta-analysis of the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) for inguinal hernia.

To evaluate the outcomes of Trans Rectus Sheath Extra-Peritoneal Procedure (TREPP) in patients undergoing elective inguinal hernia repair. In compliance with PRISMA statement standards, electronic databases were searched to identify all studies reporting the outcomes of TREPP in patients undergoing elective inguinal hernia repair. The outcomes of interest included recurrence, chronic pain, haematoma, and wound infection. Proportion meta-analysis model was constructed to quantify the risk of postoperative complications and direct comparison meta-analysis model was constructed to compare the outcomes of TREPP and other open techniques. Random-effects modelling was applied to calculate pooled outcome data. Seven studies enrolling 1891 patients undergoing TREPP were included. The mean operative time was 26min (95% CI 15-36). Pooled analyses showed that TREPP was associated with 3.00% (95% CI 1.00-6.00%) risk of recurrence, 3.00% (95% CI 2.00-6.00%) risk of chronic pain, 8.00% (95% CI 0.00-20.00%) risk of haematoma, and 3.00% (95% CI 0.00-6.00%) risk of wound infection. The results remained consistent through subgroup analysis of patients with primary hernias and those with recurrent hernias. Analysis of a limited number of comparative studies showed no difference between TREPP and Lichtenstein technique in terms of recurrence (OR 1.57, P = 0.26) and chronic pain (OR 1.16, P = 0.59). The best available evidence suggests that TREPP may be a promising technique for elective repair of inguinal hernias as indicated by low risks of recurrence, chronic pain, haematoma, and wound infection. The available evidence is limited to studies from a same country conducted by almost the same research group which may affect generalisability of the findings. Moreover, there is a lack of comparative evidence on outcomes of TREPP versus other techniques highlighting a need for high-quality randomised controlled trials for definite conclusions. Although the available evidence is not adequate for definite conclusions, the results of current study can be used for sample size calculation and power analysis in future trials.

Feasibility and relatability of cultural adaptation amongst conflict-affected populations

Cultural aspects, such as cultural values and specific stressors, need to be considered in intervention development of care.11Resnicow, K. (1999). Cultural sensitivity in public health: defined and demystified. Ethnicity & Disease. One study looked at the relevance and necessity of cultural adaptation in mental health interventions, and the results were conclusive. They found that for populations the intervention was not designed for, treatment was less effective than for the target population.22Benish, S.G. (2011). Culturally adapted psychotherapy and the legitimacy of myth: a direct-comparison meta analysis. Journal of Counselling Psychology. Existing mental health programs well established in developed countries, with a low-threshold for quality care and a flexible delivery of the care, have shown to be less effective for marginalized populations and refugees, where linguistic and cultural barriers still exist. These barriers include limited understanding of treatment, a lack of knowledge on the healthcare systems in host countries, and the lack of interpreters or programs available in their native language.33Marrone, S. (2007). Understanding barriers to health care: a review of disparities in health care services among indigneous populations. International Journal of Circumpolar Health. A promising approach for culturally-informed treatment are short skills-training interventions, designed to help participants better cope with stress and build up resilience to successfully deal with new challenges. START NOW is an evidence-based integrative skills training program and an effective treatment for vulnerable adolescents in demanding situations. We designed a total of eleven characters and fifthteen storylines that reflect the negative experiences commonly experienced by the target beneficiaries, and then conducted content testing to identify the most relatable among them. By conducting content testing, we can culturally adapt the START NOW program to meet the needs of Persian and Afghans migrants, informed by the very community that the program seeks to help. The results identified the six most relatable characters and twelve most relatable storylines, which will go on to feature in START NOW intervention sessions, and improve outcomes in testing the adapted program's efficacy with participants in Switzerland. This study provided a greater understanding of the challenges and emotions experienced by Persian and Afghan migrants, and enables us to design an effective, culturally-relevant treatment to address symptoms of poor mental health amongst this population. We can now replicate this process when adapting evidence-based treatments for other populations in need.

TP6.1.8 Meta-analysis and trial sequential analysis of three-port versus four-port laparoscopic cholecystectomy (Level 1 Evidence)

Abstract Aims to compare the outcomes of three-port and four-port laparoscopic cholecystectomy. Methods In compliance with PRISMA statement standards, electronic databases were searched to identify all comparative studies investigating outcomes of three-port versus four-port laparoscopic cholecystectomy. Two techniques were compared using direct comparison meta-analysis model. The risks of type 1 or type 2 error in the meta-analysis model were assessed using trial sequential analysis model. The certainty of the available evidence was assessed using GRADE system. Random effects modelling was applied to calculate pooled outcome data. Results Analysis of 2524 patients from 17 studies showed that three-port and four-port laparoscopic cholecystectomy techniques were comparable in terms of operative time (MD:-0.13,P=0.88), conversion to open operation (OR:0.80,P=0.43), gallbladder perforation (OR:1.43,P=0.13), bleeding from gallbladder bed (OR: 0.81, P = 0.34), bile duct injury (RD: 0.00, P = 0.97), iatrogenic visceral injury (RD:-0.00,P=0.81), bile or stone spillage (OR:1.67,P=0.08), port site infection (OR:0.90,P=0.76) and need for reoperation (RD:-0.00,P=0.94). However, the three-port technique was associated with lower VAS pain score at 12 hours (MD:-0.66,P<0.00001) and 24 hours (MD:-0.54,P<0.00001) postoperatively, shorter length of hospital stay (MD: -0.09, P = 0.41), and shorter time to return to normal activities (MD:-0.79,P=0.02). Conclusions Robust evidence (Level 1 with high certainty) suggests that in an elective setting with uncomplicated cholelithiasis as indication for cholecystectomy, three-port laparoscopic cholecystectomy is comparable with the four-port technique in terms of procedural and morbidity outcomes and may be associated with less postoperative pain, shorter length of hospital stay and shorter time to return to normal activities.

Urine Biomarkers for the Diagnosis of Bladder Cancer: a Network Meta-Analysis.

To identify effective urine biomarkers for bladder cancer diagnosis. This meta-analysis was conducted following the guidelines of the Meta-Analyses (PRISMA) statement. Relevant studies were searched from the PubMed, Embase, and Cochrane Library databases. Heterogeneity tests were performed using Q statistics and I2 tests to determine the use of the random or fixed effects model. A direct comparison meta-analysis and network meta-analysis were conducted. The effect values are presented as odds ratios and 95% confidence intervals. Sensitivity analysis and consistency tests were performed. Fifty-eight studies with 12,038 participants were included. Direct comparison meta-analysis showed statistically significant differences in bladder cancer antigen (BTA) trak vs. nuclear matrix protein 22 (NMP22), BTA stat vs. urine cytology (UC), and fluorescence in situ hybridization (FISH) vs. UC, among the sensitivity indicators. Among the specificity indicators, there were statistically significant differences in BTA trak vs. UC, ImmunoCyt (immunocyte) vs. NMP22, and BTA stat vs. FISH. Among the positive predictive indicators, NMP22 vs. UC, BTA stat vs. UC, and FISH vs. NMP22 showed statistically significant differences. Among the negative predictive indicators, the differences in FISH vs. UC, FISH vs. NMP22, and hyaluronidase 1 (HYAL-1) vs. UC were statistically significant. Among the accuracy indicators, FISH vs. NMP22, FISH vs. UC, and HYAL-1 vs. UC showed statistically significant differences. Network meta-analysis showed that HYAL-1, urothelial carcinoma associated 1 (UCA1) and survivin had the highest sensitivity, while UC had the lowest sensitivity. The specificity of UC, FISH, and HYAL-1 was the highest, while that of UCA1 was the lowest. In terms of positive predictive indicators, UC, FISH, and HYAL-1 had the highest positive predictive value, while the BTA group had the lowest positive predictive value. In terms of negative predictive indicators, HYAL-1, UCA1, and survivin had the highest negative predictive value, while UC had the lowest negative predictive value. In terms of accuracy indicators, HYAL-1, UCA1, and survivin had the highest accuracy, while UC had the lowest accuracy. HYAL-1 and survivin are suitable urine biomarkers for bladder cancer diagnosis.

Meta-analysis and trial sequential analysis of three-port vs four-port laparoscopic cholecystectomy (level 1 evidence).

To compare the outcomes of three-port and four-port laparoscopic cholecystectomy. In compliance with PRISMA statement standards, electronic databases were searched to identify all comparative studies investigating outcomes of three-port vs four-port laparoscopic cholecystectomy. Two techniques were compared using direct comparison meta-analysis model. The risks of type 1 or type 2 error in the meta-analysis model were assessed using trial sequential analysis model. The certaintyof evidence was assessed using GRADE system. Random effects modelling was applied to calculate pooled outcome data. Analysis of 2524 patients from 17 studies showed that both techniques were comparable in terms of operative time (MD:- 0.13, P = 0.88), conversion to open operation (OR:0.80, P = 0.43), gallbladder perforation (OR: 1.43, P = 0.13), bleeding from gallbladder bed (OR:0.81, P = 0.34), bile duct injury (RD: 0.00, P = 0.97), iatrogenic visceral injury (RD: - 0.00, P = 0.81), bile or stone spillage (OR:1.67, P = 0.08), port site infection (OR: 0.90, P = 0.76), port site hernia (RD: 0.00, P = 0.89), port site haematoma (RD: - 0.01, P = 0.23), port site seroma (RD: 0.00, P = 1.00), and need for reoperation (RD: - 0.00, P = 0.94). However, the three-port technique was associated with lower VAS pain score at 12h (MD: - 0.66, P < 0.00001) and 24h (MD: - 0.54, P < 0.00001) postoperatively, shorter length of hospital stay (MD:-0.09, P = 0.41), and shorter time to return to normal activities (MD: - 0.79, P = 0.02). Trial sequential analysis confirmed that the meta-analysis was conclusive with no significant risks of type 1 or type 2 error. Robust evidence (level 1 with high certainty) suggests that in an elective setting with uncomplicated cholelithiasis as indication for cholecystectomy, three-port laparoscopic cholecystectomy is comparable with the four-port technique in terms of procedural and morbidity outcomes and may be associated with less postoperative pain, shorter length of hospital stay and shorter time to return to normal activities.

The Efficacy and Safety of Acetaminophen in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundOral and intravenous (IV) acetaminophen has become widely used perioperatively as part of a multi-modal pain management protocol for primary total joint arthroplasty (TJA). The purpose of our study is to evaluate the efficacy and safety of acetaminophen in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. MethodsWe searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published prior to September 2019 on acetaminophen in primary TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of acetaminophen. ResultsIn total, 1287 publications were critically appraised yielding 17 publications representing the best available evidence for analysis. Oral and IV acetaminophen demonstrates the ability to safely reduce postoperative pain and opioid consumption during the inpatient hospital stay. No evidence was available to assess the efficacy and safety of oral acetaminophen after discharge. ConclusionModerate evidence supports the use of oral and IV acetaminophen as a non-opioid adjunct for pain management during the inpatient hospitalization. Strong evidence supports the safety of oral and IV acetaminophen when appropriately administered to patients undergoing primary TJA. Although there is lack of robust evidence for use of acetaminophen following discharge, it remains a low-cost and low-risk option as part of a multimodal pain regimen.

The Efficacy and Safety of Opioids in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundOpioids are frequently used to treat pain after total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of opioids in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management. MethodsThe MEDLINE, EMBASE, and Cochrane Central Register of controlled trials were searched for studies published before November 2018 on opioids in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of opioids. ResultsPreoperative opioid use leads to increased opioid consumption and complications after TJA along with a higher risk of chronic opioid use and inferior patient-reported outcomes. Scheduled opioids administered preemptively, intraoperatively, or postoperatively reduce the need for additional opioids for breakthrough pain. Prescribing fewer opioid pills after discharge is associated with equivalent functional outcomes and decreased opioid consumption. Tramadol reduces postoperative opioid consumption but increases the risk of postoperative nausea, vomiting, dry mouth, and dizziness. ConclusionModerate evidence supports the use of opioids in TJA to reduce postoperative pain and opioid consumption. Opioids should be used cautiously as they may increase the risk of complications, such as respiratory depression and sedation, especially if combined with other central nervous system depressants or used in the elderly.

The Efficacy and Safety of Gabapentinoids in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundGabapentinoids are commonly used as an adjunct to traditional pain management strategies after total joint arthroplasty (TJA). The purpose of this study is to evaluate the efficacy and safety of gabapentinoids in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management. MethodsThe MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched for studies published prior to November 2018 on gabapentinoids in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of gabapentinoids. ResultsIn total, 384 publications were critically appraised to provide 13 high-quality studies regarded as the best available evidence for analysis. In the perioperative period prior to discharge, pregabalin reduces postoperative opioid consumption, but gabapentinoids do not reduce postoperative pain. After discharge, gabapentin does not reduce postoperative pain or opioid consumption, but pregabalin reduces both postoperative pain and opioid consumption. ConclusionModerate evidence supports the use of pregabalin in TJA to reduce postoperative pain and opioid consumption. Gabapentinoids should be used with caution, however, as they may lead to an increased risk of sedation and respiratory depression especially when combined with other central nervous system depressants such as opioids.

Histamine2-Receptor Antagonists, Proton Pump Inhibitors, or Potassium-Competitive Acid Blockers Preventing Delayed Bleeding After Endoscopic Submucosal Dissection: A Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) was commonly used for en bloc resection in gastric cancer and adenoma with the risk of delayed bleeding after ESD. We conducted a direct and indirect comparison meta-analysis to evaluate the best choice in preventing post-ESD bleeding among proton pump inhibitors (PPIs), histamine2-receptor antagonists (H2RAs), and the most widely used potassium-competitive acid blocker, vonoprazan. Methods: The Pubmed, Cochrane Library, and Embase were searched for randomized trials. We pooled odds ratios (OR) for preventing post-ESD bleeding using meta-analysis. Results: Sixteen randomized trials met the inclusion criteria including 2,062 patients. Direct comparisons showed slightly significant efficacy in PPIs rather than H2RAs in preventing post-ESD bleeding [OR: 1.83; 95% confidence interval (CI): 1.10 to 3.05] and vonoprazan was better than PPIs (OR: 0.46; 95% CI: 0.25 to 0.86). The adjusted indirect comparison indicated vonoprazan was superior to H2RAs (OR: 0.30, 95% CI: 0.12 to 0.74). In subgroup analysis, PPIs had similar efficacy as H2RAs in 4 weeks, while PPIs were better than H2RAs in 8 weeks’ treatment (OR: 1.91; 95% CI: 1.08 to 3.40). The superiority of vonoprazan than PPIs was more significant in combination therapy (OR: 0.18; 95% CI: 0.04 to 0.69). There was a significant difference in vonoprazan for 8 weeks of medication (OR: 0.44; 95% CI: 0.21 to 0.92). Conclusions: The effects of vonoprazan is better than PPIs than H2RAs in preventing bleeding after ESD. When vonoprazan combined with mucosal protective antiulcer drug in treatment or used in 8 weeks of medication, the efficacy may be even better.

Comparative efficacy and safety for different chemotherapy regimens used concurrently with thoracic radiation for locally advanced non-small cell lung cancer: a systematic review and network meta-analysis

BackgroundIt remains unknown which is the most preferable regimen used concurrently with thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue.MethodsPubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Overall survival (OS) data was the primary outcome of interest, and progression-free survival (PFS), and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs).Results14 RCTs with a total of 2975 patients randomized to receive twelve categories of treatments were included in the meta-analysis. Direct comparison meta-analysis showed that etoposide-cisplatin (EP) was more effective than paclitaxel-cisplatin/carboplatin (PC) in terms of OS (HR = 0.85, 95% CI: 0.77–0.94) and PFS (HR = 0.66, 95% CI: 0.47–0.95). In network meta-analysis, all regimen comparisons did not produce statistically significant differences in survival. Based on treatment ranking of OS and the benefit-risk ratio, S-1-cisplatin (SP) was likely to be the most preferable regimen for its best efficacy and low risk of causing SAEs. Uracil/tegafur-cisplatin (UP) and pemetrexed-cisplatin/carboplatin (PP) were ranked the second and third respectively. Gemcitabine-cisplatin (GP) and PC + Cetuximab (PC-Cet) appeared to be the worst and second-worst regimens for their poor efficacy and poor tolerability.ConclusionsBased on efficacy and tolerability, SP is likely to be the most preferable regimen used concurrently with thoracic radiation for locally advanced NSCLC, followed by UP and PP. Further direct head-to-head studies are needed to confirm these findings.

Safety and efficacy of active and passive immunotherapy in mild-to-moderate Alzheimer's disease: A systematic review and network meta-analysis.

The objective of this study was to systematically review and conduct a direct and network meta-analysis of randomized controlled trials that have examined the clinical safety and efficacy of using passive and active immunotherapies in Alzheimer's disease (AD). (1) Is amyloid-based immunotherapy in patients with mild-to-moderate AD associated with more efficacy benefits compared to placebo? (2) Which immunotherapy agent is associated with more comparative benefit? (3) Is passive or active immunotherapy associated with more benefits? A systematic review of published randomized controlled trials was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Review methods and meta-analysis: Two reviewers independently selected the studies, extracted the data and assessed risk of bias. Important AD cognitive scales as clinical efficacy outcomes were ADAS-cog, CDR and MMSE whereas edema, neoplasms and mortality were included as safety outcomes. A direct comparison meta-analysis using a random effect model and a network (direct and indirect) comparison was conducted to calculate mean differences in treatment effects, SUCRA and ranking probabilities for each medicine per safety and efficacy outcome. Quality of network results were assessed using GRADE methodology. Thirteen RCT-assessed patients with mild-to-moderate AD were included in the final analysis. The results showed that immunotherapies compared with placebo produced a statistically, but not clinically significant, improvement in ADAS-cog (MD=-0.39; 95% CI -0.42, -0.35, P=0.00) and MMSE. In terms of safety, the rate of ARIA-E was significantly higher with monoclonal antibodies. Solanezumab and AN1792 (vaccine) were the drugs of choice both from efficacy and safety perspectives. In terms of efficacy, the review showed a statistically, but not clinically significant, improvement in favor of immunotherapy versus placebo. Further clinical trials are required to demonstrate any cognitive benefits of immunotherapies in mild-to-moderate AD.